Gaze direction is an important social cue that can induce shifts of attention (Friesen & Kingstone, 1998). Recent studies have found that familiarity of male faces modulates the degree that gaze directs attention in females but not in males (Deaner et al., 2006). It is possible that this familiarity effect is unique to female viewers, however, it is also possible that the familiarity effect occurs in both genders but is strongest when the gaze is displayed by the opposite gender. We tested these two hypotheses by manipulating the familiarity of both male and female face-cues. In the ‘familiar’ condition, participants were exposed to, and tested on, information about the identity and background of a male and a female face. In the ‘unfamiliar’ condition, the same participants were exposed to different male and female faces, but were not given any information about them. Each trial began with the presentation of a familiar or unfamiliar face with the eyes diverted to the left or right. Participants discriminated a target letter presented in the gazed-at or the non-gazed-at location. The face-target SOA ranged from 147–1200 ms and the gaze direction did not predict the target location. The analysis revealed an interaction between familiarity, target location (gazed-at vs. not-gazed-at), face gender, and participant gender. In the unfamiliar condition, gaze cueing was greater when the genders of the face and participant were the same than when the genders were different. The reverse pattern was found for familiar faces: gaze cueing was largest when the face and participant genders were different than when the genders were the same. Results suggest that the extent to which both women and men are sensitive to gaze direction depends on familiarity and the gender of the observer in relation to the gender of other individuals.